AIDS will never be curable using anti-retroviral drugs alone, and developing any cure for the disease will be 鈥渧ery difficult鈥�, says Robert Siliciano, an internationally renowned HIV researcher at Johns Hopkins University, Maryland.
However, drugs can contain the virus sufficiently to offer patients the hope of leading a normal life and less toxic versions must now be developed, he told the XIV International AIDS Conference in Barcelona.
The problem is a group of immune cells called CD4+ T cells, which become infected with HIV when the virus enters the body. Most of these cells are killed quickly. But if infected activated cells revert to a 鈥渞esting鈥� state, they can form a reservoir for the virus that effectively lasts a lifetime, Siliciano says.
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鈥淭he virus can establish a state of silent infection in long-lived immunocytes 鈥� in memory cells, whose biological function is to survive for years,鈥� he says. 鈥淚t looks as if it will never be possible to eradicate this reservoir with anti-retrovirals alone.鈥�
And he adds: 鈥淥ther approaches would be difficult because the infected cells are essentially indistinguishable from uninfected cells. It鈥檚 going to be very hard to specifically target them.鈥�
Pure information
Siliciano and colleagues were the first to discover the CD4+ HIV 鈥渞eservoir鈥�: 鈥淲hen we initially discovered it we weren鈥檛 sure whether it would eventually decay or not. Now it has become clear that that reservoir does not decay.鈥�
It is almost impossible to identify which CD4+ cells are infected with the virus because they do not appear to be making any HIV RNA or protein. 鈥淭herefore the only difference between a latently infected cell and its uninfected counterpart is a little bit of extra DNA representing the HIV genome. Essentially, the virus is persisting as pure information,鈥� he says.
Even new types of drug will not deal with the reservoir problem, he says. On Monday, an international team, including researchers at the Chelsea and Westminster Hospital, London, revealed positive results from a Phase III trial of a drug called T-20, which is designed to block HIV from entering CD4+ cells. Existing AIDS drugs only work once the HIV virus has entered cells.
Toxic problem
鈥淭hese new classes of drug that are coming out are clearly going to be extremely important,鈥� says Siliciano. 鈥淏ut they will not help with the problem of viral reservoirs. None of these drugs will affect the reservoir once it is established.鈥�
But highly active antiretroviral therapy (HAART) can stop the progression of the virus in its tracks, he stresses: 鈥淚n principle, this offers the chance of a normal life to everyone living with HIV.鈥�
鈥淲e now have drugs powerful enough to stop the evolution of the virus. The problem is that these same drugs are quite toxic. We now need to understand and overcome the problems of toxicity.鈥�